Fig. 1. Scaffold-mediated delivery of genome-engineered anticytokine cells.

(A) CRISPR-Cas9 genome editing was used to engineer stem cells containing a synthetic gene circuit that expresses the IL-1Ra, an inhibitor of IL-1, in response to activation of the chemokine (C-C) motif ligand 2 (Ccl2) promoter. NF-κB, nuclear factor κB. (B) Cells were engineered to form stable cartilaginous constructs on three-dimensional (3D) woven scaffolds in chondrogenic media. Constructs were tested in vitro to assess on-off dynamics in response to changing levels of IL-1. (C) To test their efficacy, these anticytokine constructs were implanted subcutaneously in K/BxN model of RA.